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. 1998 Oct;95(2):219–225. doi: 10.1046/j.1365-2567.1998.00574.x

Unresponsiveness of CD4-8+/- thymocytes to lectin stimulation in LEC mutant rats.

T Sakai 1, T Agui 1, K Wei 1, M Oka 1, H Hisaeda 1, H Nagasawa 1, K Himeno 1, K Matsumoto 1, W Kaichun 1
PMCID: PMC1364308  PMID: 9824479

Abstract

A mutant strain of rat, LEC, shows a novel arrest of T-cell maturation from CD4+8+ to CD4+8-, but not to CD4-8+ cells in the thymus. The responsible mutant locus is designated the thid, which was acted upon in a recessive manner of inheritance. We found that LEC rat thymocytes failed to respond to interleukin (IL)-1, IL-6 and IL-7 in the presence of the mitogenic lectins, Allo A or concanavalin A (Con A). The unresponsiveness appeared to be due to unresponsiveness to the lectin stimulation rather than because of cytokine stimulation. Normal rat CD4-8+/- (consisting of CD4-8+ and CD4-8- thymocytes), CD4+/-8- (consisting of CD4+8- and CD4-8- thymocytes), and CD4-8- thymocyte subsets normally responded to mitogenic stimulation, while CD4+8+ thymocytes did not. In contrast, all LEC rat CD4-8+/-, CD4+/-8-, CD4-8- and CD4-8+ thymocytes did not respond to the mitogenic stimulation, suggesting that the unresponsiveness of the CD4-8+/- thymocytes seems to be responsible for the unresponsiveness of whole thymocytes in LEC rats. LEC rat CD4-8+/- thymocytes normally expressed Con A receptor (R), lymphocyte function-associated antigen-1 (LFA-1), and CD45, which are thought to be important molecules for lectin stimulation. When backcross rats from (F344xLEC)F1xLEC were examined, the phenotype for the thid mutation correlated with the [3H]thymidine deoxyribose (TdR) incorporation level in response to Con A stimulation; thymocytes from backcross rats showing +/thid phenotype responded to Con A stimulation normally, whereas thymocytes from backcross rats showing thid/thid phenotype showed significantly lower responsiveness compared with +/thid rats. However, in WKAH.C-thid congenic rat thymocytes that carry the thid mutation, the responsiveness to mitogenic stimulation was comparable to that of normal rat thymocytes. These results suggest that a defect in responsiveness to mitogenic stimulation in LEC rat thymocytes is controlled by multiple genetic loci and the thid locus is one of the important loci for the development of this abnormal phenotype.

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Selected References

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  1. Agui T., Oka M., Yamada T., Sakai T., Izumi K., Ishida Y., Himeno K., Matsumoto K. Maturational arrest from CD4+8+ to CD4+8- thymocytes in a mutant strain (LEC) of rat. J Exp Med. 1990 Dec 1;172(6):1615–1624. doi: 10.1084/jem.172.6.1615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Agui T., Sakai T., Himeno K., Matsumoto K. Bone marrow-derived progenitor T cells convey the origin of maturational arrest from CD4+CD8+ to CD4-CD8+ thymocytes in LEC mutant rats. Eur J Immunol. 1991 Sep;21(9):2277–2280. doi: 10.1002/eji.1830210942. [DOI] [PubMed] [Google Scholar]
  3. Agui T., Sakai T., Matsumoto K. Ontogeny of T cell maturation in LEC mutant rats which bear a congenital arrest of maturation from CD4+CD8+ to CD4+CD8- thymocytes. Eur J Immunol. 1991 Oct;21(10):2537–2541. doi: 10.1002/eji.1830211034. [DOI] [PubMed] [Google Scholar]
  4. Bernabeu C., Carrera A. C., De Landázuri M. O., Sánchez-Madrid F. Interaction between the CD45 antigen and phytohemagglutinin. Inhibitory effect on the lectin-induced T cell proliferation by anti-CD45 monoclonal antibody. Eur J Immunol. 1987 Oct;17(10):1461–1466. doi: 10.1002/eji.1830171012. [DOI] [PubMed] [Google Scholar]
  5. Brideau R. J., Carter P. B., McMaster W. R., Mason D. W., Williams A. F. Two subsets of rat T lymphocytes defined with monoclonal antibodies. Eur J Immunol. 1980 Aug;10(8):609–615. doi: 10.1002/eji.1830100807. [DOI] [PubMed] [Google Scholar]
  6. Chang J. F., Thomas C. A., 3rd, Kung J. T. Induction of high level IL-2 production in CD4+8- T helper lymphocytes requires post-thymic development. J Immunol. 1991 Aug 1;147(3):851–859. [PubMed] [Google Scholar]
  7. DeLuca D., Mizel S. B. I-A-positive nonlymphoid cells and T cell development in murine fetal thymus organ cultures: interleukin 1 circumvents the block in T cell differentiation induced by monoclonal anti-I-A antibodies. J Immunol. 1986 Sep 1;137(5):1435–1441. [PubMed] [Google Scholar]
  8. Dissen E., Fossum S. Chromosomal localization of the genes encoding rat CD4, CD8alpha, and CD8beta. Immunogenetics. 1996;44(4):312–314. doi: 10.1007/BF02602563. [DOI] [PubMed] [Google Scholar]
  9. Grusby M. J., Johnson R. S., Papaioannou V. E., Glimcher L. H. Depletion of CD4+ T cells in major histocompatibility complex class II-deficient mice. Science. 1991 Sep 20;253(5026):1417–1420. doi: 10.1126/science.1910207. [DOI] [PubMed] [Google Scholar]
  10. Helle M., Brakenhoff J. P., De Groot E. R., Aarden L. A. Interleukin 6 is involved in interleukin 1-induced activities. Eur J Immunol. 1988 Jun;18(6):957–959. doi: 10.1002/eji.1830180619. [DOI] [PubMed] [Google Scholar]
  11. Herbelin A., Machavoine F., Schneider E., Papiernik M., Dy M. IL-7 is requisite for IL-1-induced thymocyte proliferation. Involvement of IL-7 in the synergistic effects of granulocyte-macrophage colony-stimulating factor or tumor necrosis factor with IL-1. J Immunol. 1992 Jan 1;148(1):99–105. [PubMed] [Google Scholar]
  12. Hünig T., Wallny H. J., Hartley J. K., Lawetzky A., Tiefenthaler G. A monoclonal antibody to a constant determinant of the rat T cell antigen receptor that induces T cell activation. Differential reactivity with subsets of immature and mature T lymphocytes. J Exp Med. 1989 Jan 1;169(1):73–86. doi: 10.1084/jem.169.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kimura S., Umetsu K., Yamashita T., Suzuki T., Arai S., Sendo F. T cell mitogenicity of a novel beta-D-galactoside-specific lectin from the beetle, Allomyrina dichotoma (allo A). Immunopharmacology. 1987 Jun;13(3):181–188. doi: 10.1016/0162-3109(87)90056-7. [DOI] [PubMed] [Google Scholar]
  14. Kroemer G. The pharmacology of T cell apoptosis. Adv Immunol. 1995;58:211–296. doi: 10.1016/s0065-2776(08)60621-5. [DOI] [PubMed] [Google Scholar]
  15. Locker J., Gill T. J., 3rd, Kraus J. P., Ohura T., Swarop M., Rivière M., Islam M. Q., Levan G., Szpirer J., Szpirer C. The rat MHC and cystathionine beta-synthase gene are syntenic on chromosome 20. Immunogenetics. 1990;31(4):271–274. doi: 10.1007/BF00204899. [DOI] [PubMed] [Google Scholar]
  16. Lotz M., Jirik F., Kabouridis P., Tsoukas C., Hirano T., Kishimoto T., Carson D. A. B cell stimulating factor 2/interleukin 6 is a costimulant for human thymocytes and T lymphocytes. J Exp Med. 1988 Mar 1;167(3):1253–1258. doi: 10.1084/jem.167.3.1253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rahemtulla A., Fung-Leung W. P., Schilham M. W., Kündig T. M., Sambhara S. R., Narendran A., Arabian A., Wakeham A., Paige C. J., Zinkernagel R. M. Normal development and function of CD8+ cells but markedly decreased helper cell activity in mice lacking CD4. Nature. 1991 Sep 12;353(6340):180–184. doi: 10.1038/353180a0. [DOI] [PubMed] [Google Scholar]
  18. Sakai T., Agui T., Matsumoto K. Maturational arrest from CD4+8+ to CD4+8- thymocytes is caused by the bone marrow-derived cells in LEC mutant rats. Immunol Lett. 1993 Oct;38(2):145–152. doi: 10.1016/0165-2478(93)90180-a. [DOI] [PubMed] [Google Scholar]
  19. Sakai T., Agui T., Muramatsu Y., Yamada T., Hisaeda H., Himeno K., Matsumoto K. Function of CD4 molecules in LEC rat thymocytes. J Vet Med Sci. 1996 Nov;58(11):1125–1127. doi: 10.1292/jvms.58.11_1125. [DOI] [PubMed] [Google Scholar]
  20. Sakai T., Agui T., Muramatsu Y., Yamada T., Matsumoto K. Dissociation of interleukin-2 production from the cell activation in response to the mitogenic lectin in peripheral CD4+ T cells of LEC mutant rats. Immunology. 1993 Jul;79(3):491–497. [PMC free article] [PubMed] [Google Scholar]
  21. Sakai Y., Kimura S., Yamashita T., Umetsu K., Suzuki T., Sendo F. A sensitive IL-1 thymocyte co-stimulator assay using a novel beta-D-galactoside specific lectin from the beetle, Allomyrina dichotoma. Microbiol Immunol. 1989;33(7):569–577. doi: 10.1111/j.1348-0421.1989.tb02007.x. [DOI] [PubMed] [Google Scholar]
  22. Sunderland C. A., McMaster W. R., Williams A. F. Purification with monoclonal antibody of a predominant leukocyte-common antigen and glycoprotein from rat thymocytes. Eur J Immunol. 1979 Feb;9(2):155–159. doi: 10.1002/eji.1830090212. [DOI] [PubMed] [Google Scholar]
  23. Takashi T., Gause W. C., Wilkinson M., MacLeod C. L., Steinberg A. D. Interleukin 1-induced maturation of progenitor thymocytes. Eur J Immunol. 1991 Jun;21(6):1385–1390. doi: 10.1002/eji.1830210609. [DOI] [PubMed] [Google Scholar]
  24. Takeda S., Gillis S., Palacios R. In vitro effects of recombinant interleukin 7 on growth and differentiation of bone marrow pro-B- and pro-T-lymphocyte clones and fetal thymocyte clones. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1634–1638. doi: 10.1073/pnas.86.5.1634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tamatani T., Kotani M., Miyasaka M. Characterization of the rat leukocyte integrin, CD11/CD18, by the use of LFA-1 subunit-specific monoclonal antibodies. Eur J Immunol. 1991 Mar;21(3):627–633. doi: 10.1002/eji.1830210314. [DOI] [PubMed] [Google Scholar]
  26. Uckun F. M., Tuel-Ahlgren L., Obuz V., Smith R., Dibirdik I., Hanson M., Langlie M. C., Ledbetter J. A. Interleukin 7 receptor engagement stimulates tyrosine phosphorylation, inositol phospholipid turnover, proliferation, and selective differentiation to the CD4 lineage by human fetal thymocytes. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6323–6327. doi: 10.1073/pnas.88.14.6323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Van Damme J., Van Beeumen J., Decock B., Van Snick J., De Ley M., Billiau A. Separation and comparison of two monokines with lymphocyte-activating factor activity: IL-1 beta and hybridoma growth factor (HGF). Identification of leukocyte-derived HGF as IL-6. J Immunol. 1988 Mar 1;140(5):1534–1541. [PubMed] [Google Scholar]
  28. Watson J. D., Morrissey P. J., Namen A. E., Conlon P. J., Widmer M. B. Effect of IL-7 on the growth of fetal thymocytes in culture. J Immunol. 1989 Aug 15;143(4):1215–1222. [PubMed] [Google Scholar]
  29. Wei K., Muramatsu Y., Sakai T., Yamada T., Matsumoto K. Chromosomal mapping of the T-helper immunodeficiency (thid) locus in LEC rats. Immunogenetics. 1997;47(1):99–102. doi: 10.1007/s002510050333. [DOI] [PubMed] [Google Scholar]
  30. Williams A. F., Galfrè G., Milstein C. Analysis of cell surfaces by xenogeneic myeloma-hybrid antibodies: differentiation antigens of rat lymphocytes. Cell. 1977 Nov;12(3):663–673. doi: 10.1016/0092-8674(77)90266-5. [DOI] [PubMed] [Google Scholar]
  31. Yamada T., Natori T., Izumi K., Sakai T., Agui T., Matsumoto K. Inheritance of T helper immunodeficiency (thid) in LEC mutant rats. Immunogenetics. 1991;33(3):216–219. doi: 10.1007/BF01719246. [DOI] [PubMed] [Google Scholar]

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